Therefore, we screened differentially expressed miRNAs clinically or pathologically relevant to the specific genetic mutations involved in rectal NETs based on the tumor grade to identify miRNA biomarkers related to prognosis and tumor behavior.
Up-regulated miR-3934-5p and down-regulated miR-4286, miR-223-3p, miR-129-5p, and miR-153-3p were characterized in tumors with high mitotic indices, in which miR-3934-5p was the only one statistically significant after adjustment. Further clustering analysis separated two main groups: (1) high mitotic index, grade 2, wild-type FBXW7, and wild-type TP53 and (2) low mitotic index, grade 1, FBXW7 mutation, and TP53 mutation. This may indicate that these miRNA contributions were mutually exclusive between the high mitotic index and FBXW7 mutation in rectal NETs. The KEGG pathway maps also confirmed the different pathway involvement in different miRNAs between FBXW7-mutated and highly mitotic-active tumors. hsa-miR-3934-5p may be closely implicated in a high mitotic index, eventually contributing to higher grade 2 tumors in rectal NETs.
Nevertheless, some conclusions emerged from our results. To our knowledge, this is the first study to identify a correlation between FBXW7 mutations and miRNAs in rectal NETs. hsa-miR-769-5p was most correlated with FBXW7 mutation and further linked to ECM-receptor interaction and lysine degradation via a KEGG analysis of target signaling pathways. hsa-miR-3934-5p may be strongly implicated in a high mitotic index, which may eventually contribute to higher grade 2 tumors in rectal NETs, whereas hsa-miR-769-5p related to FBXW7 mutation may be involved in grade 1 tumors and is likely to play a role in suppressing rectal NET progression.
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